A surgeon, regardless of specialty, in the course of a procedure is concerned with the repair of damaged tissues and vessels. Restoring tissue and circulation integrity is critical in the positive outcome of a procedure regardless of whether the damage was the result of trauma or the surgical procedure itself.
The oldest method of joining damaged tissues is the use of mechanical securements such as clamps, staples or sutures. Mechanical tissue securements have proved to suffer a variety of limitations. Mechanical securements require significant skill and are slow to apply. Further, mechanical securements are ineffectual in a number of highly vascularized organs such as the liver, lung and brain. A mechanical securement also often leaks along the line of joinder and itself causes additional trauma to surrounding tissue. These characteristics of a mechanical securement further slow the surgical procedure and healing time.
The inability of mechanical securements to staunch blood loss associated with trauma has cost innumerable lives and led to research intent on overcoming the difficulties associated with the mechanical securement. These efforts have focused on the use of an adhesive or glue capable of bonding tissue surfaces together rapidly while promoting or at least not inhibiting normal healing.
A common class of tissue adhesives is fibrin-based and contains a concentrate of fibrinogen and thrombin. The fibrin adhesives are typically two-component adhesives that when mixed together react to simulate the last stages of the clot-forming cascade. The resulting clot adheres to tissue and bridges a gap therebetween until healing can occur. However, fibrin-based adhesives have met with limited success owing to low strength and the risk of infection associated with harvesting fibrin from pooled human blood. Blood-born hepatitis and HIV, along with other possible diseases, are a matter of great concern. The use of autologous plasma to prepare a fibrin sealant overcomes this difficulty, yet is time consuming and of little value in instances of direct trauma such as that inflicted in automobile accidents or gunshot wounds.
Glues based on gelatin cross-linked with an aldehyde have also met with limited success. Representative of this class of glues are gelatin-resorcinol cross-linked with formaldehyde (GRF) or glutaraldehyde (GRFG). While gelatin-based glues have been extensively studied and shown to generally be effective, these compositions have met with limited success owing to the use of hot gelatin solutions, tissue irritation associated with the aldehyde, and the criticality of handling procedures needed to obtain proper cross-linking at the joinder site.
A variety of adhesives found in nature, such as barnacle glue, appear to have excellent polymerization and mechanical properties. However, development of natural product based glues has been hampered by the ability to purify appreciable quantities of such materials, as well as persistent concerns about the triggering of an immune response by foreign glycoproteins.
Owing to the above-described limitations, considerable development effort has been directed towards finding a suitable synthetic composition operative as a tissue glue. To this end, cyanoacrylates, polyurethanes, polymethylmethacrylates, among other synthetic polymers, have been investigated as tissue glues. Each of these synthetic compositions has met with limited success owing to a variety of problems such as toxic degradation products, poor mechanical properties, cure exotherms that overheat surrounding tissue, and not being biodegradable.
Tissue welding or laser light induced tissue glue cure have also been investigated and proven only partly successful. Laser associated tissue repair has met with limited success owing to transmural thermal injury and the need for a highly skilled and well equipped surgical team.
In view of the enormous development efforts that have taken place, there are few available tissue glue compositions that meet the requirements of sufficient mechanical strength, biocompatibility and bioavailability, in addition to handling properties consistent with a variety of surgical settings. Upon consideration of these stringent requirements for a tissue glue, the cross-linking of a water soluble protein by a biocompatible aldehyde appears to be one of the few possible solutions. Illustrative of developments in this area include U.S. Pat. Nos. 5,385,606 and 6,310,036. While the adhesives disclosed in these patents afford satisfactory biocompatibility and bioabsorbability, the usage properties and mechanical strength properties of these prior art tissue adhesives are not optimal. Thus, there exists a need for a tissue adhesive sealant that is not only biocompatible, but also is a well-defined cure and affords a bond line that exceeds in strength physiological forces encountered in the course of healing.